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Influence of Tyrosine Kinase Inhibitors and Everolimus on TGFβ1 and TGF-β Receptor 2 in Squamous Cell Carcinoma Cells

Lena Huber1, Manuel Thomas Knüttel2, Benedikt Kramer2

  • 1Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany; lena.huber@umm.de.

Anticancer Research
|July 26, 2024
PubMed
Abstract

Insights

Targeted therapies like nilotinib and dasatinib impact transforming growth factor-β (TGF-β) signaling in head and neck squamous cell carcinoma (HNSCC) cells. These drugs altered TGFβ1 and TGF-β receptor type 2 (TGFβR2) expression, influencing cancer cell characteristics.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Transforming growth factor-β (TGF-β) signaling is implicated in cancer development, with dual roles in promoting tumorigenesis and tumor suppression.
  • Tyrosine kinase inhibitors (TKIs) like nilotinib, dasatinib, erlotinib, gefitinib, and everolimus are used in treating various cancers, including head and neck squamous cell carcinoma (HNSCC).

Purpose of the Study:

  • To investigate the in vitro effects of approved TKIs on the expression of TGFβ1 and its receptor, TGF-β receptor type 2 (TGFβR2).
  • To analyze these effects in both HPV-negative and HPV-positive HNSCC cell lines.

Main Methods:

  • Three HNSCC cell lines were treated with nilotinib, dasatinib, erlotinib, gefitinib, and everolimus at 20 μmol/l.
  • Expression levels of TGFβ1 and TGFβR2 were quantified using enzyme-linked immunosorbent assay (ELISA) at 24, 48, 72, and 96 hours post-treatment.
  • Results were compared against a chemonaive control group.

Main Results:

  • Statistically significant alterations (p<0.05) in TGFβ1 and TGFβR2 expression were observed in all treated HNSCC cell lines compared to controls.
  • Most TKIs increased TGFβR2 expression while decreasing TGFβ1 levels.
  • Everolimus demonstrated an inverse effect, altering both TGFβR2 and TGFβ1 expression in the opposite direction.

Conclusions:

  • TGFβ1 and TGFβR2 are expressed in cultured HNSCC cell lines.
  • The tested TKIs (nilotinib, dasatinib, erlotinib, gefitinib, and everolimus) demonstrably impact TGFβ1 and TGFβR2 expression in vitro, suggesting a role in modulating TGF-β signaling pathways within HNSCC.
Keywords:
Head and neck squamous cell carcinoma (HNSCC)tyrosine kinase inhibitors

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